scholarly journals Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

2021 ◽  
Vol 11 ◽  
Author(s):  
E. Eduardo Sanchez-Castro ◽  
Cecilia Pajuelo-Reyes ◽  
Rebeca Tejedo ◽  
Bárbara Soria-Juan ◽  
Rafael Tapia-Limonchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Effective Treatment ◽  
Muscle Regeneration ◽  
Therapeutic Potential ◽  
Cost Effective ◽  
Skeletal Muscle Regeneration ◽  
Paracrine Effects ◽  
Allogeneic Mscs ◽  
Cost Effective Treatment ◽  
Anti Inflammatory

Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 1473-1488
Author(s):  
Seong-Eun Byun ◽  
Changgon Sim ◽  
Yoonhui Chung ◽  
Hyung Kyung Kim ◽  
Sungmoon Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Regeneration ◽  
Therapeutic Potential ◽  
Human Adipose Tissue ◽  
Treated Group ◽  
Skeletal Muscle Regeneration ◽  
Biopsy Punch ◽  
Healthy Control ◽  
Muscle Defect

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

scholarly journals The COX-2 pathway is essential during early stages of skeletal muscle regeneration

2004 ◽  
Vol 287 (2) ◽  
pp. C475-C483 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Kristy M. Kegley ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Cellular Processes ◽  
Early Stages ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal anti-inflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2−/− muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2−/− muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease.

scholarly journals The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 708 ◽  
Author(s):  
Marielle Saclier ◽  
Michela Lapi ◽  
Chiara Bonfanti ◽  
Giuliana Rossi ◽  
Stefania Antonini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Muscle Regeneration ◽  
Tissue Repair ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Dead Cell ◽  
Myogenic Cells ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Macrophages (MPs) are immune cells which are crucial for tissue repair. In skeletal muscle regeneration, pro-inflammatory cells first infiltrate to promote myogenic cell proliferation, then they switch into an anti-inflammatory phenotype to sustain myogenic cells differentiation and myofiber formation. This phenotypical switch is induced by dead cell phagocytosis. We previously demonstrated that the transcription factor Nfix, a member of the nuclear factor I (Nfi) family, plays a pivotal role during muscle development, regeneration and in the progression of muscular dystrophies. Here, we show that Nfix is mainly expressed by anti-inflammatory macrophages. Upon acute injury, mice deleted for Nfix in myeloid line displayed a significant defect in the process of muscle regeneration. Indeed, Nfix is involved in the macrophage phenotypical switch and macrophages lacking Nfix failed to adopt an anti-inflammatory phenotype and interact with myogenic cells. Moreover, we demonstrated that phagocytosis induced by the inhibition of the RhoA-ROCK1 pathway leads to Nfix expression and, consequently, to acquisition of the anti-inflammatory phenotype. Our study identified Nfix as a link between RhoA-ROCK1-dependent phagocytosis and the MP phenotypical switch, thus establishing a new role for Nfix in macrophage biology for the resolution of inflammation and tissue repair.

scholarly journals MicroRNA-223-3p promotes skeletal muscle regeneration by regulating inflammation in mice

2020 ◽  
Vol 295 (30) ◽  
pp. 10212-10223 ◽  
Author(s):  
Naixuan Cheng ◽  
Chang Liu ◽  
Yulin Li ◽  
Shijuan Gao ◽  
Ying-Chun Han ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Early Stage ◽  
Skeletal Muscle Regeneration ◽  
Inflammatory Factors ◽  
Regeneration Ability ◽  
Macrophage Phenotype ◽  
Anti Inflammatory

After injury, the coordinated balance of pro- and anti-inflammatory factors in the microenvironment contribute to skeletal muscle regeneration. However, the underlying molecular mechanisms regulating this balance remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in inflammation and muscle regeneration. miRNA-Seq transcriptome analysis of mouse skeletal muscle revealed that miR-223-3p is upregulated in the early stage of muscle regeneration after injury. miR-223-3p knockout resulted in increased inflammation, impaired muscle regeneration, and increased interstitial fibrosis. Mechanistically, we found that myeloid-derived miR-223-3p suppresses the target gene interleukin-6 (Il6), associated with the maintenance of the proinflammatory macrophage phenotype during injury. Administration of IL-6-neutralizing antibody in miR-223-3p-knockout muscle could rescue the impaired regeneration ability and reduce the fibrosis. Together, our results reveal that miR-223-3p improves muscle regeneration by regulating inflammation, indicating that miRNAs can participate in skeletal muscle regeneration by controlling the balance of pro- and anti-inflammatory factors in the skeletal muscle microenvironment.

Therapeutic Potential of Human Tonsil-Derived Stem Cell for Skeletal Muscle Regeneration

Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. S23-S24
Author(s):  
S. Park ◽  
Y. Choi ◽  
N. Jung ◽  
J. Kim ◽  
B. Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Therapeutic Potential ◽  
Skeletal Muscle Regeneration ◽  
Human Tonsil
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